PLK1 Target Analysis Report Summary
About the Target
PLK1, a protein kinase, plays various roles in different cellular processes and pathways.
In the cell cycle progression, PLK1 phosphorylates and translocates GTSE1 into the nucleus, which then binds to p53 and shuttles it from the nucleus to the cytoplasm. This leads to the inactivation of p53 and checkpoint recovery [1].
PLK1 also interacts with Smad-3 and stabilizes HEF1, allowing it to interact with Aur-A. This interaction is essential for the disassembly of primary cilia before mitosis. In the absence of PLK1, Smad-3 generates a HEF1 destruction complex, leading to the degradation of HEF1 and preventing its interaction with Aur-A in the G0/G1 phase [2].
Up-regulated PLK1 inhibits the damage repair mechanism and releases cells from G2/M arrest with damaged DNA. It phosphorylates and degrades several proteins associated with DNA repair and G2/M arrest, such as Chk-2, p53, MYT1, WEE1, and claspin. PLK1's phosphorylation of RAD51 activates BRCA1/2 and recruits the RAD51-NBS complex to repair DNA damage. Additionally, PLK1 phosphorylation blocks the G1/S transition, providing time for damage repair [3].
In pancreatic cancer, a combination therapy involving a small molecule PLK1 inhibitor and microRNA-34a is illustrated as a potential treatment option [4].
PLK1 is also involved in regulating chromosome condensation, MTOC fragmentation, and LISD recruitment in mammalian oocytes. It dissociates C-NAP1, allowing MTOC components to fragment and form bipolar spindles. PLK1 is required for the recruitment of Aurora A and TACC3 in oocytes. The absence of PLK1 leads to defects in chromosome condensation, MTOC failure, and abnormal spindle formation in oocytes [5].
These viewpoints highlight the diverse functions of PLK1 in different cellular pathways, including cell cycle regulation, DNA damage response, cancer treatment, and reproductive processes.
Based on the provided context information, here are some key viewpoints regarding PLK1:
PLK1 plays a role in substrate recognition and mitotic progression [6].
PLK1 has two classes of phospho-substrates: one including proteins 'X' and 'Y' (e.g., NEDD1) and the other containing a hydrophobic amino acid residue near the pS/pT residue, such as protein 'P' (e.g., PBIP1) [6].
PLK1Wt (wild type) can bind to both categories of PBD-substrates [6].
PLK1AAD does not bind to protein 'P'-like substrates [6].
PLK1AM does not bind to any substrates [6].
Following mitochondrial depolarization, PINK accumulates on the outer mitochondrial membrane and recruits Parkin from the cytosol. The activation of Parkin on Ser 65 by PINK enables the formation of ubiquitin chains, leading to the recruitment of the autophagic machinery [7].
Damaged mitochondria are engulfed by autophagosomes, which later fuse with lysosomes to form autophagolysosomes [7].
During cell division, PLK1 activates Parkin, allowing it to bind to Cdc20 or Cdh1 and facilitate the destruction of substrates controlled by these two APC/C activators [7].
These viewpoints cover various aspects of PLK1's function in mitotic progression, its role in substrate recognition, and its involvement in mitochondrial health and cell division.
Figure [1]
Figure [2]
Figure [3]
Figure [4]
Figure [5]
Figure [6]
Figure [7]
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